EP1200317B1 - A device for spray dispensing a composition for topical application comprising vitamin e and essential fatty acids - Google Patents
A device for spray dispensing a composition for topical application comprising vitamin e and essential fatty acids Download PDFInfo
- Publication number
- EP1200317B1 EP1200317B1 EP00947999A EP00947999A EP1200317B1 EP 1200317 B1 EP1200317 B1 EP 1200317B1 EP 00947999 A EP00947999 A EP 00947999A EP 00947999 A EP00947999 A EP 00947999A EP 1200317 B1 EP1200317 B1 EP 1200317B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- fatty acids
- composition
- vitamin
- use according
- essential fatty
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/046—Aerosols; Foams
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
- A61K8/355—Quinones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/55—Phosphorus compounds
- A61K8/553—Phospholipids, e.g. lecithin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/58—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
- A61K8/585—Organosilicon compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/678—Tocopherol, i.e. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
- A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
Definitions
- the present invention relates to the field of dermatology and dermocosmesis.
- the invention relates to a device that is capable of dispensing in the form of spray a composition based on vitamin E and essential fatty acids.
- vitamin E i.e. ⁇ -tocopherol and derivatives thereof are substances which are widely used in the cosmetic industry, by virtue of their properties as antioxidants and free radicals scavengers, in the preparation of formulations for combating or preventing unsightly skin conditions or for slowing down the cellular aging.
- ⁇ -tocopherol is also capable of protecting the skin from UV radiation, as it absorbs in the 295-315 nm wavelength range, thereby preventing the formation of erythema due to exposure to the sunlight or to artificial UV sources.
- free ⁇ -tocopherol is photolabile and oxidizable in presence of air and the compositions that contain it do not show enough stability to storage.
- Essential fatty acids are fatty acids that cannot be synthesized by human beings and therefore need to be introduced as part of the alimentary diet in order to ensure the good health of the body.
- the essential fatty acids in the vertebrates and consequently in the human beings are linoleic acid, from which derives the Omega-6 ( ⁇ -6) series ( ⁇ -linolenic acid, dihomo- ⁇ -linolenic acid and arachidonic acid) and the ⁇ -linoleic acid, from which derives the Omega-3 ( ⁇ -3) series (eicosapentaenoic and docosahexaenoic acid).
- the ⁇ -6 and ⁇ -3 acids are polyunsaturated fatty acids, also known as PUFA (Polyunsaturated Fatty Acids) which can be taken with the alimentary diet although vertebrates may also synthesize them starting from essential fatty acids.
- PUFA Polyunsaturated Fatty Acids
- the linoleic acid plays a fundamental role in the normal constitution of the interlamellar lipidic component of the horny layer of epidermis and hence in the correct barrier function of the horny layer. In fact, it represents about 50 % of the esterified fatty acids in the ceramides of the lamellar bodies and the ceramides are the most important class of the interlamellar lipids. Indeed, the ceramides build up a structure of single o double lipid layers into which the other classes of interlamellar lipids do insert themselves, i.e. the aliphatic chains of the free fatty acids and of cholesterol.
- the interlamellar lipids bond also to the protein envelope of the horny layer cells, thus forming a coating having a cementing function and a function of selective permeability, contributing in an important way to provide the skin with compactness, elasticity and plasticity.
- the problem underlying the present invention is that of providing a composition for topical use containing both vitamin E and essential fatty acids (EFA) or ⁇ -6- or ⁇ -3-polyunsaturated fatty acids, that has satisfying storability properties.
- EFA essential fatty acids
- a device for spray delivering a composition for topical application comprising a collapsible container which in turn is enclosed in a spray bomb filled with pressurized fluid, that causes said composition to be dispensed in finely atomized form, characterized in that said composition comprises a low vapor pressure vehicle consisting of one or more volatile silicones, one or more essential (EFA) or polyunsaturated ⁇ -6 or ⁇ -3 (PUFA) fatty acids or one or more oils that contain them and vitamin E.
- EFA essential
- PUFA polyunsaturated ⁇ -6 or ⁇ -3
- the volatile silicones are chosen among pentamer cyclomethicone, tetramer cyclomethicone, hexamethyldisiloxane and mixtures thereof.
- pentamer cyclomethicone is particularly preferred.
- Nitrogen, carbon dioxide and preferably air are used as the pressurized fluid.
- oils containing essential fatty acids or PUFAs are chosen, preferably, among grape seed, maize, rice, soybean, safflower, borage, Oenothera biennis (evening primrose), sunflower and blackcurrant oil.
- Vitamin E may be used as d- ⁇ -tocopherol or as a mixture of the two d and 1 enantiomers of ⁇ -tocopherol or as a mixture of other tocopherols ( ⁇ , ⁇ , ⁇ , ⁇ , ⁇ ).
- composition for topical application contained in the device according to the invention can advantageously include other compounds having antioxidant activity, such as lipoic acid, coenzyme Q 10 , vitamin A and derivatives thereof, in particular retinal and retinol palmitate and fat-soluble derivative of vitamin C, in particular ascorbyl palmitate.
- antioxidant activity such as lipoic acid, coenzyme Q 10 , vitamin A and derivatives thereof, in particular retinal and retinol palmitate and fat-soluble derivative of vitamin C, in particular ascorbyl palmitate.
- lecithin represents a source of phospholipids which readily integrate in the membranes of the epidermal cells, giving rise to an increase of the skin elasticity and plasticity. Moreover, lecithin contributes to the stabilization of the overall composition, by virtue of its emulsifying action.
- a fragrance may be added to the composition.
- composition contained in the device according to the invention may also serve as vehicle for various pharmaceutical or cosmetic active principles of lipophilic nature, for which it enhances the absorption through the skin.
- the composition therein contained may comprise other compounds provided with absorption properties in the field of ultraviolet radiation, such as miroxil, salicylates, p-aminobenzoates, benzophenones, cinnamates, derivatives of dibenzoylmethane, derivatives of benzylidenecamphor, naphthoates, gallates and mixtures thereof, or physical filters, such as for example titanium dioxide, zinc oxide, barium sulfate, calcium carbonate and magnesium carbonate.
- other compounds provided with absorption properties in the field of ultraviolet radiation such as miroxil, salicylates, p-aminobenzoates, benzophenones, cinnamates, derivatives of dibenzoylmethane, derivatives of benzylidenecamphor, naphthoates, gallates and mixtures thereof, or physical filters, such as for example titanium dioxide, zinc oxide, barium sulfate, calcium carbonate and magnesium carbonate.
- composition contained in the device according to the invention is preferably the one reported hereinbelow (the percentages are by weight on the total weight of the composition): Vitamin E 5-30 % Oil rich in EFAs and/or PUFAs 4-30 % Ascorbyl palmitate 0,2-3 % Coenzyme Q 10 0,01-2 % Lipoic acid 0,01-2 % Retinol palmitate 0,01-2 % Lecithin 0-2 % Pentamer cyclomethicone q.s. to 100 %
- oil rich in EFAs and/or PUFAs means an oil having a content of essential fatty acids (EFA) and/or of ⁇ -6 or ⁇ -3 polyunsaturated fatty acids of at least 50 % in weight.
- EFA essential fatty acids
- the filling of the collapsible container with the above reported composition can be advantageously carried out under a nitrogen atmosphere, in order to ensure the absence of air inside the container and accordingly absolutely prevent any possible phenomenon of oxidation involving the active principles of the composition.
- EP-A-0 711 540 discloses an anti-againg cream comprising vitamin E, blackcormnt oil and a volatile silicone oil with the registered trade mark "Dow Corning Fluid 345®”.
- Spray dispensing devices made up of a bomb provided inside it with a collapsible container are for example described in patent application FR 2 436 085.
- the composition By making use of the device according to the present invention, it is possible to apply the composition in a finely atomized way, thus forming a film endowed with properties of remarkable bio-adhesiveness with respect to the skin, whereby an immediate and effective absorption of the active principles therein contained is promoted. All this occurs not only thanks to the action of the atomizer, but, also and above all, thanks to the specific properties of the vehicle.
- the most important advantage achieved by the device according to the present invention consists in the possibility of maintaining throughout the whole period of storage of the composition (at least two years) the integrity of the active principles, vitamin E and essential fatty acids, by the device protecting such active principles from oxidations and degradations caused by atmospheric oxygen and by light.
- Vitamin E in particular, kept aside from entering into contact with air and light, is capable of carrying out at its best its antioxidant action and of preventing the EFA and PUFA degradation.
- tocopherol of the above-mentioned other natural compounds having an antioxidant activity, further increases the stability of the composition of the device according to the invention, thanks to the synergistic action brought about by such compounds with tocopherol in preventing the oxidation of the essential fatty acids. Furthermore, the great amount of tocopherol has a protective effect with respect to the other antioxidant substances contained in the composition, allowing them to fully carry out for a long time their typical biological action.
- Another advantage of the device according to the invention consists in the absence of preservatives in the composition.
- a device according to the invention is schematically shown, which is comprised of a collapsible container 1, which contains the above described composition, connected to a valve 2 onto which a sprayhead 3 acts; the collapsible container 1 is in turn enclosed inside a bomb 4, with valve 2 cramped to the lip of the bomb 4, and the gap between the inner wall of the bomb 4 and the container 1 is filled with a pressurized gas.
- Vitamin E 20 Grape seed oil 10 % Ascorbyl palmitate 1 % Coenzyme Q 10 0,1 % Lipoic acid 0,1 % Retinol palmitate 0,1 % Pentamer cyclomethicone q.s. to 100 %
- the gap between the container 1 and the inner wall of the bomb 4 was filled with air at 10 atmospheres. Then, the solution obtained by dispersing in cyclomethicone the other above-listed compounds was introduced into the collapsible container 1 under a flow of nitrogen , according to methods well known in the art.
- Vitamin E 13 Grape seed oil 5 % Ascorbyl palmitate 1 % Coenzyme Q 10 0,1 % Lipoic acid 0,1 % Retinol palmitate 0,1 % Pentamer cyclomethicone q.s. to 100 %
- Example 1 The above-reported composition was prepared as for Example 1 and the filling of the device was carried out in the same way as for Example 1.
- composition is particularly well suited for the prevention of erythema and sunburns due to exposure to the sun or to other sources of UV radiation.
- conventional sun-oil and sun-creams formulations the above reported one, besides the shield action with respect to UV radiation, also has an emollient, moisturizing and protective action for the skin not only with respect to UV radiation but also to other physical-chemical or atmospheric agents. Moreover, it is able to slow down the cellular aging processes, which are on the contrary accelerated by the skin exposure to sun radiation or UV radiation in general.
- the vitamin E contained in the composition exerts an action of sun filter for UVB radiation and protects the cells of the epidermis and dermis from the damages due to repeated overexposure to UVA radiation (photoageing and photocarcinogenesis).
- Vitamin E 20 Grape seed oil 7 % APEROXID TLA® 2% Ascorbyl palmitate 1 % Coenzyme Q 10 0,1 % Lipoic acid 0,1 % Retinol palmitate 0,1 % Pentamer cyclomethicone q.s. to 100 %
- APEROXID TLA® is a product marketed by BIOCHIM S.r.l. (Italy), which contains more than 50% b.w. of soy lecithin, 10-15% of mixed natural tocopherols, 8-10% ascorbyl palmitate and 1-5% citric acid.
- the lecithin phospholipids contained in this formulation are easily integrated in the membranes of the epidermal cells and bring about a further increase of the elasticity and plasticity of the skin.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT1999MI001747A IT1313595B1 (it) | 1999-08-03 | 1999-08-03 | Dispositivo per erogazione spray di una composizione per applicazionetopica comprendente vitamina e e acidi grassi essenziali. |
ITMI991747 | 1999-08-03 | ||
PCT/EP2000/007168 WO2001009000A1 (en) | 1999-08-03 | 2000-07-26 | A device for spray dispensing a composition for topical application comprising vitamin e and essential fatty acids |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1200317A1 EP1200317A1 (en) | 2002-05-02 |
EP1200317B1 true EP1200317B1 (en) | 2003-06-18 |
Family
ID=11383495
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP00947999A Expired - Lifetime EP1200317B1 (en) | 1999-08-03 | 2000-07-26 | A device for spray dispensing a composition for topical application comprising vitamin e and essential fatty acids |
Country Status (11)
Country | Link |
---|---|
EP (1) | EP1200317B1 (it) |
JP (1) | JP2003506116A (it) |
AT (1) | ATE243146T1 (it) |
AU (1) | AU773768B2 (it) |
CA (1) | CA2379776C (it) |
DE (1) | DE60003434T2 (it) |
DK (1) | DK1200317T3 (it) |
ES (1) | ES2200897T3 (it) |
IT (1) | IT1313595B1 (it) |
PT (1) | PT1200317E (it) |
WO (1) | WO2001009000A1 (it) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10024413A1 (de) * | 2000-05-19 | 2001-12-06 | Mika Pharma Gmbh | Pharmazeutische und/oder kosmetische Zubereitung |
US6949247B2 (en) | 2000-12-28 | 2005-09-27 | Unilever Home & Personal Care Usa Division Of Conopco, Inc. | Stable skin care compositions containing a retinoid and a retinoid booster system |
DE10111053A1 (de) * | 2001-03-06 | 2002-09-12 | Beiersdorf Ag | Wirkstoffkombinationen aus alpha-Liponsäure und Biochinonen |
DE10111039A1 (de) * | 2001-03-06 | 2002-09-12 | Beiersdorf Ag | Verwendung von Wirkstoffkombinationen aus alpha-Liponsäure und dermatologisch verträglichen Substanzen, die Lichtabsorption im UV-A-Bereich und/oder UV-B-Bereich zeigen, zur Herstellung von kosmetischen oder dermatologischen Zubereitungen zur Behandlung und/oder Prophylaxe der Symptome der intrinsischen und/oder extrinsischen Hautalterung sowie zur Behandlung und Prophylaxe der schädlichen Auwirkungen ultravioletter Strahlung auf die Haut |
ITBS20010027A1 (it) * | 2001-03-23 | 2002-09-23 | Gen Topics Srl | Principio attivo a base di acido lipoico ed acidi grassi polienolici |
US6589541B2 (en) | 2001-05-18 | 2003-07-08 | Classified Cosmetics, Inc. | Sprayable beautifying composition |
JP2004224742A (ja) * | 2003-01-23 | 2004-08-12 | Umeken:Kk | 皮膚外用剤 |
DE102004041270A1 (de) * | 2004-08-26 | 2006-03-02 | Merz Pharma Gmbh & Co. Kgaa | Ein Kapillar- Wirksystem enthaltende Zusammensetzungen mit anwendungsbezogener Differenzierbarkeit und deren Verwendung |
EA015246B1 (ru) | 2006-02-21 | 2011-06-30 | Мэри Кэй, Инк. | Неводная композиция стабильной аскорбиновой кислоты и способ ее приготовления |
IT1393056B1 (it) * | 2008-09-22 | 2012-04-11 | Bio Lo Ga Srl | Uso di vitamina e o suoi derivati per il controllo di artropodi |
US8440237B2 (en) | 2009-04-27 | 2013-05-14 | Mary Kay Inc. | Botanical anti-acne formulations |
FR2980975B1 (fr) * | 2011-10-05 | 2016-08-26 | Bhat Gilles Andre Yves | Nouvelle composition dermatologique comprenant du tocopherol, un macerat huileux de fleurs de calendula dans de l'huile de rose musque, du palmitate de retinol et de l'ubiquinone |
WO2013096485A1 (en) | 2011-12-19 | 2013-06-27 | Mary Kay Inc. | Combination of plant extracts to improve skin tone |
EP3116469B1 (en) | 2014-03-10 | 2018-10-03 | Mary Kay, Inc. | Skin lightening compositions |
FR3054133B1 (fr) * | 2016-07-20 | 2019-08-16 | Ste De Courtage Et De Diffusion - Codif International | Compositions cosmetiques comprenant des composes biomineraux et utilisations correspondantes pour la protection de la peau contre les rayonnements ultraviolets |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2838192A1 (de) * | 1978-09-01 | 1980-03-06 | Rhen Beteiligung Finanz | Behaelter zur aufnahme und abgabe von fluessigen und pastoesen produkten |
FR2726762B1 (fr) * | 1994-11-10 | 1997-01-17 | Oreal | Composition cosmetique ou dermatologique sous forme d'une dispersion d'une phase huileuse dans une phase aqueuse stabilisee a l'aide de particules de gel cubique et son procede d'obtention |
-
1999
- 1999-08-03 IT IT1999MI001747A patent/IT1313595B1/it active
-
2000
- 2000-07-26 EP EP00947999A patent/EP1200317B1/en not_active Expired - Lifetime
- 2000-07-26 JP JP2001514212A patent/JP2003506116A/ja active Pending
- 2000-07-26 WO PCT/EP2000/007168 patent/WO2001009000A1/en active IP Right Grant
- 2000-07-26 DK DK00947999T patent/DK1200317T3/da active
- 2000-07-26 ES ES00947999T patent/ES2200897T3/es not_active Expired - Lifetime
- 2000-07-26 PT PT00947999T patent/PT1200317E/pt unknown
- 2000-07-26 CA CA2379776A patent/CA2379776C/en not_active Expired - Lifetime
- 2000-07-26 AT AT00947999T patent/ATE243146T1/de active
- 2000-07-26 DE DE60003434T patent/DE60003434T2/de not_active Expired - Lifetime
- 2000-07-26 AU AU61600/00A patent/AU773768B2/en not_active Expired
Also Published As
Publication number | Publication date |
---|---|
ATE243146T1 (de) | 2003-07-15 |
ITMI991747A1 (it) | 2001-02-03 |
DK1200317T3 (da) | 2003-10-13 |
WO2001009000B1 (en) | 2001-09-13 |
WO2001009000A1 (en) | 2001-02-08 |
AU773768B2 (en) | 2004-06-03 |
EP1200317A1 (en) | 2002-05-02 |
PT1200317E (pt) | 2003-11-28 |
ITMI991747A0 (it) | 1999-08-03 |
JP2003506116A (ja) | 2003-02-18 |
DE60003434D1 (de) | 2003-07-24 |
DE60003434T2 (de) | 2004-05-06 |
IT1313595B1 (it) | 2002-09-09 |
AU6160000A (en) | 2001-02-19 |
CA2379776C (en) | 2011-04-05 |
ES2200897T3 (es) | 2004-03-16 |
CA2379776A1 (en) | 2001-02-08 |
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